1. Field of the Invention
This invention is related to immunologically active agents capable of inducing immune responses in humans and other animals which result in protection against infection by malaria parasites and more particularly to the protection of humans against the human malaria parasite Plasmodium falciparum.
2. Description of the Prior Art
The need for vaccines to relieve the current global resurgence of malaria is clear. Because immunity in malaria is stage specific, vaccines are being developed against each stage in the malarial life cycle: sporozoites, the mosquito stage that initiates infection in man; asexual erythrocytic parasites, the stage that causes the disease; and gametes, the stage that transmits the infection to mosquitoes. One area of interest is a sporozoite vaccine which, if effective, would prime the immune system to kill sporozoites innoculated by the mosquito and thus prevent the subsequent stages responsible for the disease in transmission of the infection to others.
Animals and man have previously been protected by injection of irradiated sporozoites. Vaccination with irradiated sporozoites is impractical, however, because of the limited supply and instability of sporozoites. Use of monoclonal antibodies led to the discovery of the major surface protein on sporozoites of Plasmodium berghei, a rodent malaria (N. Yoshida, R. S. Nussenzweig, P. Potocnjak, et al, Science 207, 71 (1980)). This protein covers the surface of the sporozoite and is referred to as the circumsporozoite (CS) protein. Injection of monoclonal antibodies to the CS protein of P. berghei completely protected mice from challenge by infected mosquitoes (P. Potocnjak, R. S. Nussenzweig, V. Nussenzweig, J. Exp. Med. 151, 1504 (1980)). Analogous CS proteins have been identified for species of monkey and human malaria, including P. falciparum, the major malaria of man (F. Santoro et al, J. Biol. Chem. 258, 3341 (1983); E. H. Nardin et al, J. Exp. Med. 156, 20 (1982)), although the structure of the P. falciparum protein was not known prior to the present invention. The gene for the CS protein of the monkey malaria, P. knowlesi, was cloned first because of the availability of large numbers of P. knowlesi sporozoites in infected mosquitoes for preparation of a cDNA library J. Ellis (L. S. Ozaki, R. W. Gwadz et al, Nature 302, 536 (1983); G. N. Godson, J. Ellis, P. Svee et al, Nature 305, 29 (1983)). This gene encoded for a protein with a repeating amino acid sequence (12 amino acids repeated 12 times) which contained the epitope that bound the protective monoclonal antibodies. This repeating epitope was the major immunogen on the protein as monoclonal antibodies blocked access of polyclonal anti-sporozoite sera to Triton X-100 solubilized protein in the immunoradiometric assay (F. Zavala, A. H. Cochrane, E. H. Nardin et al, J. Exp. Med. 157, 1947 (1983)).
However, there remains a need for an antigenic material related to the CS protein of a human malaria parasite since antibodies previously prepared against this repeating epitope from monkey parasites are not reactive with human malaria parasites.